EP2744509B1 - Verwendung von interferon-beta zur behandlung von kreisrundem haarausfall - Google Patents

Verwendung von interferon-beta zur behandlung von kreisrundem haarausfall Download PDF

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Publication number
EP2744509B1
EP2744509B1 EP12745842.0A EP12745842A EP2744509B1 EP 2744509 B1 EP2744509 B1 EP 2744509B1 EP 12745842 A EP12745842 A EP 12745842A EP 2744509 B1 EP2744509 B1 EP 2744509B1
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EP
European Patent Office
Prior art keywords
interferon beta
treatment
alopecia areata
use according
composition
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Not-in-force
Application number
EP12745842.0A
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English (en)
French (fr)
Other versions
EP2744509A1 (de
Inventor
Hans-Günther GRIGOLEIT
Ivan G. Ivanov
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Tigo GmbH
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Tigo GmbH
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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/21—Interferons [IFN]
    • A61K38/215—IFN-beta
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth

Definitions

  • the present invention relates to a medicament for the treatment of alopecia areata (AA).
  • AA alopecia areata
  • AA hair loss disease
  • the prevalence (cases at any given point in time) in population is 0.1 - 0.2 %. About 1.7% of the population presents at least one episode of AA during their life.
  • the gender distribution indicates a 1:1 male to female distribution, with a peak incidence (44 %) in the age group 15 to 29 years. 30 % of patients will eventually progress to alopecia totalis (54 % of children and 24 % of adults). The proportion of patients presenting with alopecia totalis declines with each decade of life.
  • the overall incidence of relapse or of experiencing another episode of AA is 86 %.
  • AA is a disease of the anagen (growth) stage hair follicles.
  • growth stage hair follicles.
  • interferon gamma mediated autoimmune disease in which the body attacks its own hair follicles and suppresses or stops hair growth.
  • T cell lymphocytes cluster around affected follicles, causing inflammation and subsequent hair loss.
  • Follicles are in a state called dystrophic anagen phase, where follicles are producing root sheath material and often hair fibres - but they are too small and aberrant to protrude above the skin epidermis.
  • AA While not life threatening, AA nonetheless has serious implications for the patient and his/her family/social group members because of its psychological and sociological backlash. Although a benign disorder, quality of life, particularly in young patients is seriously impaired, mainly by altering self-perception, self-esteem and social life interference.
  • Schmutz discloses in "Expert Response: Interferon beta and Hair Loss" (Nouvelles Dermatticians, vol. 28, no. 4 part 1, 2009, page 212 ) that treatment with interferon beta may cause diffuse alopecia.
  • Chang et al. postulate that interferon beta secreted from human hair dermal papilla cells inhibits the growth of outer root sheath cells cultured in vitro (Biochemical and Biophysical Research Communications, vol. 290, no. 3, 1 january 2002, pages 1133-1138 ).
  • US 5 709 853 A is directed to pharmaceutical compositions for atopic disease comprising interferon beta as an active ingredient.
  • interferon beta as a medicament in the treatment of AA.
  • Interferons function as messengers responsible for the communication between cells to induce defence-mechanisms in order to eradicate pathogens or tumor cells. These proteins are produced when pathogens such as bacteria, viruses or tumor cells have been detected in the body by the immune system.
  • Interferon beta is a type I interferon produced by fibroblasts and endothelial cells. Interferon beta is mainly involved in the immune response against infections. There are three different interferon beta sources: interferon beta may either be derived from mammalian cells (interferon beta-1a) or from E.coli (interferon beta-1b). Furthermore, there exists human interferon beta.
  • interferon beta is useful as a medicament in the treatment of AA
  • interferon alpha which is the other type I interferon is known to be capable to induce AA
  • interferon gamma plays a crucial role in the pathogenesis of AA as, e.g. it is described as a biomarker of the disease, or that its presence in human skin grafts promotes hair loss.
  • interferon beta as a medicament in the treatment of AA according to the present invention the hair loss associated with AA can be reduced or even stopped.
  • interferon beta interacts with the high interferon gamma levels in the affected skin area or the body as a whole. Without wishing to be bound by this theory, this interaction may be the reason for the beneficial effect of interferon beta in the treatment of AA.
  • the type of AA that can be treated by administering the above mentioned interferon beta can be any AA selected from the group consisting of alopecia areata (patchy hair loss), alopecia areata totalis (hair loss of the total scalp) and alopecia areata universalis (total hair loss expanding over the entire body).
  • the interferon beta of the present invention may be administered to the subject suffering from AA topically or systemically.
  • AA pattern hair loss
  • local administration is preferred, whereas in case of AA universalis systemical administration seems to be preferable.
  • AA totalis either local or systemical administration is preferred.
  • said administration is preferable achieved by administering the interferon beta formulated in an ointment, a lotion, a gel, a spray, a plaster (sustained or non-sustained release plaster) etc.
  • the formulation can comprise liposomes or nanoparticles as carrier structures for the interferon beta.
  • the effective interferon beta dose range for treatment of AA is from 10 to 200 ⁇ g/day, preferably in the range of from 20 to 150 ⁇ g/day.
  • Preferably said dose is split up in 3 to 5 dose units applied separately during the day.
  • the treatment duration depends on the result achieved and may vary in the range of from 1 to 6 weeks.
  • 4.5 - 30 ⁇ g interferon beta-1b are admininstered topically 5 times daily up to 4 weeks.
  • dermal penetration is preferably enhanced by applying ultrasound (sonophoresis) to the treated areas.
  • ultrasound sonophoresis
  • interferon beta is administered to the subject to be treated systemically this is done by infusion, subcutaneous or intramuscular injection, preferably.
  • the effective interferon beta dose range for treatment of AA is from 0.1 to 125 ⁇ g/day, preferably in the range of from 1 to 20 ⁇ g/day.
  • said dose is administered on a daily basis.
  • said dose is not administered on a daily basis but every 2 nd day, 3 times a week or only in one dosage unit a week.
  • the treatment duration depends on the result achieved and may vary in the range of from 1 to 6 weeks.
  • 15 - 750 ⁇ g human interferon beta are administered up to 6 days per infusion.
  • 0.25 ⁇ g interferon beta-1 b is administered subcutaneously every 2 nd day.
  • 8.8-22 ⁇ g interferon beta-1a is administered subcutaneously 3 times a week.
  • 30 ⁇ g interferon beta-1 a is administered intramuscularly once a week.
  • interferon beta for use as a medicament in the treatment of AA according to the present invention may be administered in combination with another active agent useful in the treatment of AA.
  • administration of interferon beta and the other active agent takes place simultaneously.
  • administration takes place sequentially or even separately within a certain period of time.
  • statins such as the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors atorvastatin, fluvastatin, pravastatin, lovastatin, simvastatin, pitavastatin and rosuvastatin.
  • HMG-CoA 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors
  • atorvastatin 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors
  • fluvastatin fluvastatin
  • pravastatin lovastatin
  • simvastatin simvastatin
  • pitavastatin rosuvastatin
  • interferon beta in the treatment of AA, namely a combination of two or more interferon betas, such as interferon beta-1 a plus an interferon beta 1 b, or interferon beta-1 a in combination with human interferon beta, or interferon beta-1b in combination with human interferon beta.
  • the two or more interferon betas are administered simultaneously. In other embodiments the administration takes place sequentially or even separately within a certain period of time.
  • compositions comprising interferon beta for use as a medicament in the treatment of AA.
  • Said compositions may comprise other active agents, such as the aforementioned other active agents useful in the treatment of AA.
  • said compositions may comprise in addition or alternatively at least one auxiliary agent selected from the group consisting of carriers, recipients, adjuvants, diluents, and disintegrants.
  • the at least one auxiliary agent may be selected from the group consisting of liposomes, nanoparticles, carboxymethyl cellulose, hydroxyethyl cellulose, mineral oil, petrolatum, glycerine, polysorbat 80, hydroxyethyl starch, dextran, and polyethylene glycol.
  • interferon beta or the use of a composition comprising interferon beta in the manufacture of a medicament for treatment of AA.
  • the present invention refers also to standard dosage units comprising or being comprised of the aforementioned compositions.
  • Preferred standard dosage units are, in case of topical administration preferably plasters, and in case of systemical administration preparations for infusion or injection (either subcutaneous or intramuscular).
  • the standard dosage unit comprises preferably 2 to 200 ⁇ g interferon beta/dosage unit, more preferably the standard dosage unit comprises 10 to 100 ⁇ g interferon beta/dosage unit.
  • the standard dosage unit comprises 5, 10, 20 or 30 ⁇ g interferon beta-1/dosage unit.
  • the standard dosage unit comprises preferably 0.1 to 125 ⁇ g interferon beta/dosage unit, more preferably the standard dosage unit comprises 1 to 20 ⁇ g interferon beta/dosage unit.
  • the standard dosage unit comprises 0.1, 1, 5, 10, 20, 30, 40 or 50 ⁇ g interferon beta-1/dosage unit.
  • an infusion preparation comprises 15 - 750 ⁇ g human interferon beta/500 ml of said preparation.
  • an injection preparation for subcutaneous injection comprises 1 ⁇ g interferon beta-1 b/ml.
  • an injection preparation for subcutaneous injection comprises 100 ⁇ g interferon beta-1a/ml.
  • an injection preparation for intramuscular injection comprises 30 ⁇ g interferon beta-1a/ml.
  • the interferon beta of the present invention is administered to a subject suffering from locally occurring AA (patchy hair loss) for a specific treatment period locally by intradermal injection at a specific dose.
  • AA pattern hair loss
  • Example 1 Extending the treatment period of Example 1 to 6 weeks results in the hair loss associated with AA being almost reduced totally. However, even in this case 1 week after termination of the treatment the subject starts suffering from increasing hair loss again.
  • interferon beta-1 b Administering interferon beta-1 b to a subject suffering from locally occurring AA (patchy hair loss) intradermally at a single daily dose of 4.5 ⁇ g interferon beta-1b per 10 cm 2 of treated area for 4 weeks results in the hair loss associated with AA being almost reduced totally. 1 week after termination of the treatment the subject starts suffering from increasing hair loss again.
  • Example 3 By extending the treatment period of Example 3 to 6 weeks at the end of the treatment period there is almost no significant hair loss identifiable. However, 1 week after termination of the treatment the subject starts suffering from increasing hair loss again.
  • interferon beta-1 b Administering interferon beta-1 b to a subject suffering from locally occurring AA (patchy hair loss) intradermally at a single daily dose of 15 ⁇ g interferon beta-1 b per 10 cm 2 of treated area for 4 weeks results in the hair loss associated with AA being almost reduced totally. However, 1 week after termination of the treatment the subject starts suffering from increasing hair loss again.
  • AA pattern hair loss
  • Example 5 By extending the treatment period of Example 5 to 6 weeks there is no significant hair loss identifiable at the end of the treatment period. However, 1 week after termination of the treatment the subject starts suffering from increasing hair loss again.
  • interferon beta-1b Administering interferon beta-1b to a subject suffering from locally occurring AA (patchy hair loss) intradermally at a single daily dose of 30 ⁇ g interferon beta-1 b per 10 cm 2 of treated area for 4 weeks results in the hair loss associated with AA being reduced totally. However, 1 week after termination of the treatment the subject starts suffering from increasing hair loss again.
  • AA pattern hair loss
  • Extending the treatment period of Example 7 to 6 weeks resulted in a prolongation of the time period after which the subject starts suffering from increasing hair loss after termination of the treatment again to 2 weeks.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Dermatology (AREA)
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  • Engineering & Computer Science (AREA)
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  • Proteomics, Peptides & Aminoacids (AREA)
  • Zoology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Claims (13)

  1. Interferon beta zur Verwendung bei der Behandlung von Alopecia areata.
  2. Interferon beta zur Verwendung nach Anspruch 1, wobei das Interferon beta Interferon beta-1a, Interferon beta-1b oder humanes Interferon beta ist.
  3. Interferon beta zur Verwendung nach Anspruch 1 oder 2, wobei der Typ der zu behandelnden Alopecia areata lokal auftretende Alopecia areata, Alopecia areata totalis oder Alopecia areata universalis ist.
  4. Interferon beta zur Verwendung nach einem der Ansprüche 1 bis 3, wobei das Interferon beta dem zu behandelnden Patienten topisch oder systemisch verabreicht wird.
  5. Interferon beta zur Verwendung nach einem der Ansprüche 1 bis 4, wobei das Interferon beta dem zu behandelnden Patienten topisch in Form einer Salbe, einer Lotion, eines Gels, eines Sprays, eines Pflasters oder eines Pflasters mit verzögerter Wirkstofffreisetzung verabreicht wird, wobei diese Verabreichungsformen wahlweise Liposome oder Nanopartikel beinhalten.
  6. Interferon beta zur Verwendung nach einem der Ansprüche 1 bis 4, wobei das Interferon beta dem zu behandelnden Patienten systemisch durch intravenöse, subkutane oder intramuskuläre Injektion verabreicht wird.
  7. Interferon beta zur Verwendung nach einem der Ansprüche 1 bis 6, wobei das Interferon beta dem zu behandelnden Patienten gleichzeitig, sequenziell oder separat zusammen mit mindestens einem anderen Wirkstoff, welcher bei der Behandlung von Alopecia areata nützlich ist, verabreicht wird.
  8. Interferon beta zur Verwendung nach Anspruch 7, wobei der mindestens eine weitere Wirkstoff, welcher bei der Behandlung von Alopecia areata nützlich ist, ein Statin ist.
  9. Zusammensetzung zur Verwendung bei der Behandlung von Alopecia areata, wobei die Zusammensetzung Interferon beta aufweist.
  10. Zusammensetzung zur Verwendung nach Anspruch 9, welche mindestens ein Hilfsmittel, ausgewählt aus der Gruppe bestehend aus Trägern, Empfängern, Hilfsstoffen, Verdünnungsmitteln und Sprengmitteln aufweist.
  11. Zusammensetzung zur Verwendung nach Anspruch 10, wobei das mindestens eine Hilfsmittel ausgewählt ist aus der Gruppe bestehend aus Liposomen, Nanopartikeln, Carboxymethylcellulose, Hydroxyethylcellulose, Mineralöl, Petrolatum, Glycerin, Polysorbat 80, Hydroxyethylstärke, Dextran und Polyethylenglycol.
  12. Zusammensetzung zur Verwendung nach einem der Ansprüche 9 bis 11, welche mindestens einen weiteren Wirkstoff, welcher bei der Behandlung von Alopecia areata nützlich ist, aufweist.
  13. Zusammensetzung zur Verwendung nach Anspruch 12, wobei der mindestens eine weitere Wirkstoff, welcher zur Behandlung von Alopecia areata nützlich ist, ein Statin ist.
EP12745842.0A 2011-08-18 2012-08-07 Verwendung von interferon-beta zur behandlung von kreisrundem haarausfall Not-in-force EP2744509B1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102011052816A DE102011052816A1 (de) 2011-08-18 2011-08-18 Verwendung von Interferon-beta zur Behandlung von Alopecia areata
PCT/EP2012/065451 WO2013023961A1 (en) 2011-08-18 2012-08-07 Use of interferon beta for the treatment of alopecia areata

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EP2744509A1 EP2744509A1 (de) 2014-06-25
EP2744509B1 true EP2744509B1 (de) 2016-07-13

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DE (1) DE102011052816A1 (de)
WO (1) WO2013023961A1 (de)

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CN110025770A (zh) * 2019-04-20 2019-07-19 长春生物制品研究所有限责任公司 一种稳定的重组人干扰素软膏及其生产方法

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JP3269125B2 (ja) * 1994-01-28 2002-03-25 東レ株式会社 アトピー性皮膚炎治療薬

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WO2013023961A1 (en) 2013-02-21
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